1. Field of the Invention
The invention relates to a new microbiological process for the production of hydroxy-heterocyclic carboxylic acids of the general formula: ##STR3## wherein R.sub.1 means a hydrogen or a halogen atom and X means a nitrogen atom or a CR.sub.2 function, wherein R.sub.2 means a hydrogen or halogen atom, by means of an aerobic biomass which utilizes nicotinic acid or its soluble salts, which starts from the corresponding heterocyclic carboxylic acid or its soluble salt.
2. Background Art
In the following, the phrase "nicotinic acid" is meant to also include its soluble salts, especially its water soluble salts, such as, sodium nicotinate as alkali salt of nicotinic acid.
These hydroxy-heterocyclic carboxylic acids are important intermediate products for the production of pharmaceutical agents. For example, 6-hydroxynicotinic acid is an important intermediate product for the production of 5,6-dichloronicotinic acid (Swiss Patent No. 664,754), which in turn represents an initial product for pharmaceutical active ingredients.
A known embodiment for a microbiological process for the hydroxylation of nicotinic acid to 6-hydroxynicotinic acid is described, for example, in European Published Patent Application No. 152,948. This process is structured so that at first microorganisms are cultivated with nicotinic acid in the presence of yeast extract and then, for the actual biotransformation, the concentration of nicotinic acid as the feedstock is selected so that the catabolism of the nicotinic acid is inhibited on the first step of the 6-hydroxynicotinic acid. This process has the drawback that the cultivation of microorganisms using nicotinic acid takes place in the presence of yeast extract with which the cell-free fermentation solution is, contaminated after the cultivation or biotransformation, which leads to a contamination of the isolated 6-hydroxynicotinic acid. Another drawback lies in that this process is performed with homogeneous (biologically pure) cultures of microorganisms that are especially susceptible to infections in large-scale fermentations.